Bacterial sepsis is a major cause of morbidity and mortality in neonates, especially those involving methicillin-resistant (MRSA). Guidelines by the Infectious Diseases Society of America recommend the vancomycin 24-h area under the concentration-time curve to MIC ratio (AUC/MIC) of >400 as the best predictor of successful treatment against MRSA infections when the MIC is ≤1 mg/liter. The relationship between steady-state vancomycin trough concentrations and AUC values (mg·h/liter) has not been studied in an Asian neonatal population. We conducted a retrospective chart review in Singapore hospitals and collected patient characteristics and therapeutic drug monitoring data from neonates on vancomycin therapy over a 5-year period. A one-compartment population pharmacokinetic model was built from the collected data, internally validated, and then used to assess the relationship between steady-state trough concentrations and AUC A Monte Carlo simulation sensitivity analysis was also conducted. A total of 76 neonates with 429 vancomycin concentrations were included for analysis. Median (interquartile range) was 30 weeks (28 to 36 weeks) for postmenstrual age (PMA) and 1,043 g (811 to 1,919 g) for weight at the initiation of treatment. Vancomycin clearance was predicted by weight, PMA, and serum creatinine. For MRSA isolates with a vancomycin MIC of ≤1, our major finding was that the minimum steady-state trough concentration range predictive of achieving an AUC/MIC of >400 was 8 to 8.9 mg/liter. Steady-state troughs within 15 to 20 mg/liter are unlikely to be necessary to achieve an AUC/MIC of >400, whereas troughs within 10 to 14.9 mg/liter may be more appropriate.

Background Hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) may limit the use of aspirin in patients with cardiovascular diseases. Aspirin desensitization, which is a resource-intensive process, can offer such patients access to aspirin through the induction of temporary tolerance to aspirin. However, there is limited information on aspirin desensitization response in patients undergoing aspirin desensitization for cardiac indications in Asia. Objective To characterize patients who have undergone aspirin desensitization, evaluate their responses to the procedure, and identify risk factor(s) associated with failure of aspirin desensitization. Methods We conducted a retrospective review of medical records of patients who underwent aspirin desensitization in Singapore General Hospital between 1 June 2014 and 31 October 2017. Chi-square or Fisher exact test were used to analyze categorical data while independent samples t test or Wilcoxon rank-sum test were used for continuous data where appropriate. Multivariate logistic regression was used to identify predictors of aspirin desensitization failure. Results All 214 patients in our study had cardiovascular indications for aspirin, with angioedema being the most common type of index reaction experienced with NSAIDs (n = 104, 48.6%). One hundred sixty-five patients (77.1%) achieved successful aspirin desensitization. In the selected sample analysis of patients with true NSAID hypersensitivity (n = 163), an index reaction of angioedema to NSAIDs was found to be significantly associated with a higher risk of failing aspirin desensitization (odds ratio, 7.21; 95% confidence interval, 1.94–26.71). Conclusion Majority of the patients who underwent aspirin desensitization in our institution were able to achieve tolerance to aspirin. An index reaction of angioedema to NSAIDs was identified as a risk factor for aspirin desensitization failure. This information can aid in the risk stratification of patients undergoing aspirin desensitization and ensure efficient resource allocation for this procedure.

Background: Amyloid diseases are hereditary and include transthyretin (TTR) amyloidosis where subunit protein mutations may occur in genes for TTR, leading to the deposition of fibrils (low molecular weight subunits (5 to 25 KD of proteins) in extracellular tissues. By reducing the formation of TTR amyloid, diflunisal, a nonsteroidal anti-inflammatory drug, can preserve the quality of life and significantly reduce disease progression. We present a case of a 61-year-old male patient with a history of ibuprofen allergy, diagnosed with TTR amyloidosis, complicated with peripheral neuropathy, cardiac, and liver amyloid. He developed bilateral mild eye swelling from the ibuprofen oral provocation test. With a similar structural backbone of carboxylic acid, he could develop pseudoallergy to diflunisal with an unknown likelihood of developing an allergic reaction. Objectives: This study aims to design successful diflunisal desensitization in a patient with TTR amyloidosis. Methods: The patient underwent a 14-step diflunisal desensitization procedure using 2 tablets of diflunisal 500 mg that was dissolved in 40 mL of sodium bicarbonate 8.4% injection to create serial 10-fold dilutions. Oral desensitization was administered in the escalation of the doses at 30-min intervals, with a starting dose of 0.1 mg until a final dose of 250 mg was reached. Results: The patient tolerated diflunisal desensitization and was continued on diflunisal treatment without any evidence of an allergic reaction. Conclusion: Diflunisal desensitization can be considered in patients with a history of ibuprofen allergy if there are no available alternative treatments. To the best of our knowledge, this is the first article describing a patient with angioedema to ibuprofen who could tolerate oral diflunisal after desensitization.

No abstract

Purpose: Combination antibiotics consisting beta-lactam and aminoglycoside are commonly utilized in the treatment of neonatal septicaemia. The aims of this study were (1) to determine safety and efficacy of the revised gentamicin dosage regimen and (2) to compare intravascular (IV) versus intramuscular (IM) route of gentamicin administration, in term of attaining peak and trough serum concentration targets. Methods: This was a retrospective study from 2012 to 2017. All neonates who received gentamicin with therapeutic drug monitoring performed were included in this study. Data for all eligible neonates were collected from electronic medical records and included demographics, serum creatinine levels, the complete gentamicin dosing and concentration history. Results: A total of 737 neonates who received the correct institutional gentamicin dosage regimen (± 5% of the intended dose) were included in this study. There were 635 trough concentrations (within 30 minutes prior to subsequent dose) and 430 peak concentrations (60 to 90 minutes post administration) included in the comparison of IV and IM route of administration. With the revised dosage regimen, 91% of peak and 98% of trough concentrations were found within therapeutic range. There was no difference in terms of proportion of trough concentrations within therapeutic range for IV as compared to IM (97.8 vs 98.6%, p = 0.556) while IM resulted in a higher proportion of peak concentrations within therapeutic range (86.1 vs 97.0%, p < 0.001). Conclusions: The current institutional gentamicin dosage regimen is safe and effective in attaining therapeutic targets. Intramuscular injection can be an alternative route of administration for gentamicin in neonates.